Warning(s)

Suicidality

Antidepressants may increase risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (18–24 years of age) with major depressive disorder and other psychiatric disorders; balance this risk with clinical need.ij Imipramine is not approved for use in pediatric patients except patients ≥6 years of age with enuresis.ab (See Pediatric Use under Cautions.)

In pooled data analyses, risk of suicidality was not increased in adults >24 years of age and apparently was reduced in adults ≥65 years of age with antidepressant therapy compared with placebo.ij

Depression and certain other psychiatric disorders are themselves associated with an increased risk of suicide.ijk

Appropriately monitor and closely observe all patients who are started on imipramine therapy for clinical worsening, suicidality, or unusual changes in behavior; involve family members and/or caregivers in this process.ijk (See Worsening of Depression and Suicidality Risk under Cautions.)

Attention Deficit Hyperactivity Disorder

Associated with a narrower margin of safety than some other therapeutic agents; use only if clearly indicated and with careful monitoring, including baseline and subsequent determinations of ECG and other parameters.

Eating Disorders

Has been used for management of eating disorders† (e.g., bulimia†, anorexia nervosa†) with equivocal results; avoid use in underweight individuals and in those exhibiting suicidal ideation.c

Bipolar Disorder

Has been used for the short-term management of acute depressive episodes in bipolar disorder†.c

TCAs associated with a greater risk of precipitating hypomania or manic episodes than other classes of antidepressants;c should always be used in combination with a mood stabilizer (e.g., lithium).h

Schizophrenia

Has been used for the management of acute depressive episodes (in combination with an antipsychotic) in patients with schizophrenia†.c

Anxiety Disorders

Has been used for the management of anxiety† (in combination with an anxiolytic, a sedative, or an antipsychotic) in patients with depression.c

Postherpetic Neuralgia

Among the drugs of choice for the symptomatic treatment of postherpetic neuralgia†.c

Insomnia

Less effective for insomnia† and associated with more serious adverse reactions than conventional hypnotics.c

Imipramine Pamoate Dosage and Administration

General

Major Depressive Disorder

Allow at least 2 weeks to elapse between discontinuance of therapy with an MAO inhibitor and initiation of imipramine and vice versa.ab Also allow at least 5 weeks to elapse when switching from fluoxetine.ab

Monitor for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustments.abijk (See Worsening of Depression and Suicidality Risk under Cautions.)

Sustained therapy may be required; administer lowest effective dosage and monitor periodically for need for continued therapy.ab

Enuresis

Tolerance (tachyphylaxis) to therapeutic effects possible with continuous administration of imipramine; consider instituting a drug-free period following an adequate therapeutic trial with favorable response.a

Long-term, chronic use not recommended; gradually discontinue therapy following a period of satisfactory response.a To minimize risk of relapse, avoid abrupt discontinuance of therapy.a

Children who relapse when the drug is discontinued may not respond to subsequent treatment with imipramine.a

Administration

Oral Administration

Administer orally in up to 4 divided doses (without regard to meals)g or as a single daily dose at bedtime to avoid daytime sedation.ab

Reserve use of Tofranil-PM capsules until recommended total daily imipramine hydrochloride dosage ≥75 mg.b Tofranil-PM usually administered once daily, but divided doses may be necessary in some patients.b Tofranil-PM should not be used in children of any age.b (See Pediatric Warnings under Cautions.)

Dosage

Available as imipramine hydrochloride or imipramine pamoate; dosage is expressed in terms of imipramine hydrochloride.abf

Individualize dosage carefully according to individual requirements and response.ab

Pediatric Patients

Enuresis

Oral

Children ≥6 years of age: Initially, 25 mg daily, administered 1 hour prior to bedtime.a If satisfactory response not obtained within 1 week, dosage may be increased to 50 mg nightly for children <12 years of age or 75 mg nightly for children ≥12 years of age.a Higher dosages provide no additional therapeutic benefit but may increase risk of adverse effects.a Maximum 2.5 mg/kg daily.a

For children who are early-night bed-wetters, better results may be obtained by administering 25 mg in midafternoon and again at bedtime.a

Adults

Major Depressive Disorder

Outpatients

Oral

Initially, 75 mg daily.ab May increase dosage to 150 mg daily and then if necessary to 200 mg daily.ab

Cautions for Imipramine Pamoate

Contraindications

Known hypersensitivity to imipramine, other dibenzazepine-derivative TCAs, or any ingredient in the formulation.ab

Warnings/Precautions

Warnings

Worsening of Depression and Suicidality Risk

Possible worsening of depression and/or emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior in both adult and pediatric patients with major depressive disorder, whether or not they are taking antidepressants; may persist until clinically important remission occurs.ijkl However, suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.ijk

Appropriately monitor and closely observe patients receiving imipramine for any reason, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments.ijk (See Boxed Warning and also see Pediatric Use under Cautions.)

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania may be precursors to emerging suicidality.jk Consider changing or discontinuing therapy in patients whose depression is persistently worse or in those with emerging suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if severe, abrupt in onset, or not part of patient’s presenting symptoms.ijk (See General under Dosage and Administration.)

Prescribe in smallest quantity consistent with good patient management to reduce risk of overdosage.aj

Cardiovascular Effects

Patients with preexisting or prior history of cardiac disease, patients with disturbed eating behaviors (e.g., purging) that result in inadequate hydration and/or compromised cardiac status, geriatric patients, and children (see Pediatric Warnings) most at risk;abc use with caution and monitor closely (e.g., perform ECG at baseline and as appropriate during therapy).abc

Children may be more sensitive to an acute imipramine overdosage than adults;ab use of high-potency preparation, Tofranil-PM, not recommended for children of any age.b (See Worsening of Depression and Suicidality Risk and also see Pediatric Use under Cautions.)

Anticholinergic Effects

Use with caution in patients for whom excess anticholinergic activity could be harmful (e.g., history of urinary retention, increased intraocular pressure, angle-closure glaucoma).ab

Seizures

Lowers seizure threshold; use with caution in patients with a history of seizures.ab

Interactions

May block hypotensive actions of clonidine, guanethidine, and similar agents.ab

Activation of Mania or Hypomania

Psychosis

Risk of manifestations of psychosis in patients with schizophrenia, particularly in patients with paranoid symptoms; decrease dosage and/or administer an antipsychotic (e.g., a phenothiazine) concomitantly.ab

Elective Surgery

Discontinue therapy several days prior to surgery whenever possible.ab

Electroconvulsive Therapy (ECT)

Possible increased ECT risks; limit to patients for whom concomitant use is essential.ab

Specific Populations

Pregnancy

Lactation

Pediatric Use

Safety and efficacy not established in treatment of enuresis in children <6 years of age or for treatment of any other disorders in children <18 years of age.ab (See Pediatric Warnings under Cautions.)

FDA warns that a greater risk of suicidal thinking or behavior (suicidality) occurred during first few months of antidepressant treatment (4%) compared with placebo (2%) in children and adolescents with major depressive disorder, OCD, or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and others).j However, a more recent meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients <19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or suicidal ideation.l No suicides occurred in these pediatric trials.jl

Carefully consider these findings when assessing potential benefits and risks of imipramine in a child or adolescent for any clinical use.ijkl (See Worsening of Depression and Suicidality Risk under Cautions.)

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.c

In pooled data analyses, a reduced risk of suicidality was observed in adults ≥65 years of age with antidepressant therapy compared with placebo.ij (See Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

Special Populations

Stability

Storage

Oral

Capsules

Tablets

Actions

Mechanism of action in the management of depression unknown but may involve inhibition of reuptake of norepinephrine and/or serotonin.ab

Mechanism of action in the treatment of enuresis is not known but may involve inhibition of urination due to anticholinergic activity, CNS stimulant activity resulting in easier arousal by the stimulus of a full bladder, and/or other mechanisms that are presently unknown.c

Associated with more frequent anticholinergic, sedative, or cardiovascular effects and weight gain than SSRIs.c

Advice to Patients

Risk of suicidality; importance of patients, family, and caregivers being alert to and immediately reporting emergence of suicidality, worsening depression, or unusual changes in behavior, especially during the first few months of therapy or during periods of dosage adjustment.ijk FDA recommends providing written patient information (medication guide) explaining risks of suicidality each time the drug is dispensed.ijk

Importance of continuing imipramine therapy even if a response is not evident within 1–3 weeks, unless directed otherwise.ab

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.ab

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses or planned surgery.ab

Importance of informing patients of other important precautionary information.ab (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Imipramine Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

10 mg*

Imipramine Hydrochloride Tablets

Par

Tofranil (with povidone)

Mallinckrodt

25 mg*

Imipramine Hydrochloride Tablets

Par

Tofranil (with povidone)

Mallinckrodt

50 mg*

Imipramine Hydrochloride Tablets

Par

Tofranil (with povidone)

Mallinckrodt

Tablets, film-coated

10 mg*

Imipramine Hydrochloride Tablets

Sandoz, Mutual, United Research

25 mg*

Imipramine Hydrochloride Tablets

Sandoz, Mutual, United Research

50 mg*

Imipramine Hydrochloride Tablets

Sandoz, Mutual, United Research

Imipramine Pamoate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

equivalent to imipramine hydrochloride 75 mg

Tofranil-PM (with parabens)

Mallinckrodt

equivalent to imipramine hydrochloride 100 mg

Tofranil-PM (with parabens)

Mallinckrodt

equivalent to imipramine hydrochloride 125 mg

Tofranil-PM (with parabens)

Mallinckrodt

equivalent to imipramine hydrochloride 150 mg

Tofranil-PM (with parabens)

Mallinckrodt

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

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